[2][4] The gameplay for Skullgirls was modeled after Marvel vs. Capcom 2: New Age of Heroes, incorporating the latter's tag team mechanics, assists, and control scheme.

[3][9][10] Skullgirls includes technical features to address system and balance problems common in fighting games, such as "infinite combo" detection and protection against "unblockable attacks".

[13] The tutorials section teaches players the gameplay fundamentals of Skullgirls, in addition to covering concepts underlying the fighting game genre as a whole.

[18][19] Skullgirls takes place in the fictional Canopy Kingdom, a country reminiscent of 1940s post-war United States, which is ruled by the Renoir royal family and plagued by the Medici mafia.

[21] Humanity has fought against many Skullgirls over the course of history, establishing agencies to build weapons to confront them, the most notable of which is Canopy Kingdom's Anti-Skullgirl Labs, a black-ops research institution spearheaded by the scientist Brain Drain.

[21][22] During the Grand War, a battle fought between the Canopy Kingdom and two neighboring nations, Queen Nancy Renoir nearly brought the world to ruin when she attempted to use the Skull Heart for the sake of peace.

[21] Seven years later, a slave girl named Marie Korbel has emerged as the newest Skullgirl and begun to terrorize the Canopy Kingdom to exact revenge against the Medici.

[21][22] The Skullgirls roster initially consisted of eight playable characters: Filia, Cerebella, Peacock, Parasoul, Ms. Fortune, Painwheel, Valentine, and Double.

Following the conclusion of the game's Indiegogo crowdfunding campaign in 2013, an additional five DLC characters were developed: Squigly,[23] Big Band,[24] Eliza,[25] Beowulf,[26] and Robo-Fortune.

[38] Ahad drew the art style and character designs based on a wide variety of his influences and inspirations, such as the works of Mike Mignola and Bruce Timm, Gainax's FLCL, Tex Avery's Red Hot Riding Hood, Capcom's Darkstalkers, and artists George Kamitani and Daisuke Ishiwatari.

[39] Ahad and Zaimont pitched Skullgirls to several companies, eventually teaming up with recently founded independent developer Reverge Labs in 2010.

[50] Contributors received various rewards, including desktop wallpapers, a digital copy of the official soundtrack, and the chance to add a background character to the game, among others.

[52][53] An additional stretch goal that would provide a free license for the game's engine, Z-Engine, to the developers of Them's Fightin' Herds (at the time called Fighting is Magic) was also funded.

[58] Senior animator Jonathan "Persona" Kim claimed that Zaimont delivered an ultimatum wherein he gave all unsatisfied employees until the end of August to leave the company.

[59] By late August, Kim, Jun, and lead animator Mariel Cartwright resigned from Lab Zero Games and individually issued statements denouncing Zaimont's actions.

[63] In February 2021, Autumn Games revealed the development of the Season 1 Pass, which included four DLC characters, a digital artbook, and an updated soundtrack.

[64] In April 2021, lead animator Mariel Cartwright and CEO Francesca Esquenazi sued Lab Zero for Mike Zaimont's wrongful termination.

[67][68] Yamane's involvement was announced by Reverge Labs in April 2011, marking the first time a Japanese composer had anchored the soundtrack for an American-developed game.

[67][68] According to Reverge Labs CEO Richard Wyckoff, the developers sought out Yamane because "[they] knew her mixture of haunting gothic themes, jazz and rock would lend itself perfectly to Skullgirls' 'Dark Deco' style.

"[67] When Reverge Labs requested Yamane to write "jazzy" music, she "played a bit with the rhythm and different sounds to try and heighten the impact and almost primal nature of the unique graphics.

[91] The game was released for the Nintendo Switch on October 22, 2019; however, the Xbox One version was postponed indefinitely "due to unforeseen development and production challenges".

[97] As a result of the move, Hidden Variable Studios promised more transparency over the game's microtransactions, namely in its gacha rates, as well as more consistent release of new content.

Maxwell McGee of GameSpot credited the ability to adjust team sizes, adding that the trade-off between strength and versatility helped to accommodate a wider skill range of players.

[109] Daniel Maniago of G4 complimented the custom assists, anti-infinite system, and online play, praising Reverge Labs for utilizing feedback from the fighting game community during development.

IGN's Ryan Clements criticized the small selection of gameplay modes, missing character move lists, and overly aggressive AI.

[110] Jordan Mallory of Joystiq reprimanded the game for its "goofy and immature" premise, sexualized art style, and unoriginal character movesets.

[123] Skullgirls sold over 50,000 copies across both platforms within ten days,[124] becoming the highest selling game on the Xbox Live Arcade upon its release[125] and third best-selling title on PlayStation Network for April 2012.

[127] According to Peter Bartholow, CEO of Lab Zero Games, Skullgirls met Japanese publisher CyberFront's lifetime sales expectations in the first two weeks of release.

[130] In 2020, after the Evolution Championship Series announced its shift to an online-only format in response to the COVID-19 pandemic, Skullgirls 2nd Encore was revealed as an inclusion in its main lineup of games, owing to its use of rollback netcode.

[135][136][137] These changes included, among other things, the removal of allusions to real world hate groups and upskirt shots of teenage fighters, toning down depictions of racial violence in the story, and deleting several illustrations from the guest art gallery.